Changes in paw oedema triggered via bradykinin B-1 and B-2 receptors in streptozotocin-diabetic rats

The present study investigated hind paw oedema mediated by bradykinin B-1 a nd B-2 receptors in streptozotocin-diabetic rats. Paw oedema induced by int raplantar (i.pl.) injection of bradykinin or the selective bradykinin B-2 r eceptor agonist, Tyrosines-bradykinin ([Tyr(8)]bradykinin) (both 3 nmol/paw ), was significantly reduced at 4 weeks after streptozotocin treatment (34 +/- 8% and 40 +/- 7%). At 6 weeks after streptozotocin, when paw oedema cau sed by substance P or prostaglandin P-2 (both 10 nmol/paw) was unchanged, i nhibition of bradykinin B-2 receptor-mediated oedema was maximal (66 +/- 6% and 72 +/- 2%, for bradykinin and [Tyr(8)]bradykinin, respectively). The s elective bradykinin B-1 receptor agonist, [des-Arg(9)]bradykinin (100 nmol/ paw), induced only slight paw oedema in non-diabetic controls. Responses to [des-Arg(9)]bradykinin were markedly enhanced 8 weeks after streptozotocin (from 0.09 +/- 0.01 to 0.38 +/- 0.05 ml), less so at 10 weeks (0.22 +/- 0. 03 ml), and returning to basal values at 12 weeks (0.11 +/- 0.03 ml). Treat ment with insulin protamine zinc (1-3 U/day/7 weeks, s.c.) did not reverse the inhibition of responses to [Tyr(8)]bradykinin or the potentiation of re sponses to [des-Arg(9)]bradykinin seen at 8 weeks. Thus, streptozotocin-ind uced diabetes induces long-lasting alterations in oedematogenic responsiven ess to kinins in the rat, characterized by marked reduction of oedema invol ving activation of bradykinin B-2 receptors, associated with enhancement of bradykinin B-1 receptor-mediated oedema. (C) 2001 Published by Elsevier Sc ience B.V.